In new drug development pipelines, there is an increasing trend to switch from “small” to “large” molecules (also known as biologics). While the FDA guidance was quite specific with their recommendations for small molecules ADME-Tox studies, there is not much currently published for these large molecules.

The Japanese PDMA guidelines 2019 issue refers to some specificity regarding their internalization and degradation pathway. They are also well known to be prone to trigger cytokine release. The so called “cytokine storm” is one of the major toxicity events to be feared.

To support R&D projects around Biologics development, I have illustrated in this post what tebu-bio can offer in terms of reagents and services, including tools to monitor cytokine release (blood derivatives and cytokine multiplex assays), and reagents to help decipher their mechanism of action and catabolism.

Following up on my series of posts based on Dr Chris Bohl’s work at Sekisui Xenotech, in this post I invite you to take a look at the work he has published, together with Dr Christopher Seib, Maciej Czerwinski, Zell Woodworth and David Buckley, Ph.D., illustrating the characterization of isolated human liver lysosomes, and validating them as test systems for in vitro assessment of catabolic stability of biologics drugs entering the cell by the endosomal–lysosomal pathway.

The term Autophagy was introduced by Christian de Duve during the Ciba Foundation Symposium on Lysosomes – which was held in London in February 1963. In 1974 he was honoured with the Nobel price in Physiology or Medicine for his pioneering research about peroxisomes and lysosomes. In 2016, once more, a pioneer in the field of autophagy research won the Nobel price: Yoshinori Ohsumi, a Japanese researcher, whose findings “led to a new paradigm in our understanding of how the cell recycles its content”.

Fig 1: The process of autophagy

Autophagy (Autophagocytosis) describes the fundamental catabolic mechanism during which cells degrade dysfunctional and unnecessary cellular components. This process is driven by the action of lysosomes and promotes survival during starvation periods as the cellular energy level can thus be maintained.

Mitochondria keep cells “healthy” in their environment. In this post, we’ll take a look at a new fluorescent assay for the monitoring of mitophagy, a process aimed at clearing damaged or superfluous mitochondria by autophagy, in mammalian cells.